One of the cardinal symptoms of Parkinson's Disease (PD) is bradykinesia (slowness of movement). Intriguingly, it has been shown that, when properly motivated, PD patients can move just as quickly as healthy people. These findings suggest that slowing of movements may stem not from an inability to move faster, but from a preference for slower movements due to an altered representation of reward and effort in the brain. Unfortunately, we know little about how the brain measures effort. Current theories implicitly assume that the altered effort representation in PD stems from an exaggerated perception of effort brought on by dopamine loss. However, it is possible that objectively, the effort associated with performing movements may be increased in PD. Here, we propose an objective measure of effort in the metabolic cost expended to perform an action. We suggest that the increased perception of effort in PD may be related to an elevated objective effort cost: the metabolic cost of performing the action. Indeed, PD patients, compared with healthy controls, exhibit greater metabolic expenditure at rest, during walking, and cycling. However, while metabolic cost has proven a useful proxy for objective effort costs in locomotion, these data are largely missing for actions involving the arm. Therefore, we propose to collect a critical set of data: the metabolic costs of reaching and isometric force production in healthy people and people afflicted with PD. We will test whether such objective costs can partly account for the altered perception of effort in PD. In Aim 1 we will quantify metabolics across a range of actions in healthy individuals. In Aim 2 we will test the idea that in both decision-making and movement-control, the brain estimates effort via the expected metabolic cost of that action. In Aim 3, we apply our framework to representation of effort in PD. We propose that the increased effort cost in PD may have an objective component: increased metabolics of force production. We will measure metabolic costs of reaching movements and isometric force production in PD, and ask whether the metabolic costs are elevated on the more affected side, and elevated for directions of action in which perception of effort is particularly asymmetric. Finally, we have recently established that a form of non-invasive cortical stimulation, inhibiting the motor cortex contralateral to the affected side, may significantly reduce perception of effort in PD. Here, we ask whether this change in perception of effort coincides with changes in metabolic cost of force production. The main contribution of our work is an objective measure of effort, the metabolic cost of producing action. We will collect a critical set of data, metabolic cost of motor control in healthy people and people suffering from PD.

R01NS096083

2017-04-01

2022-03-31